Interleukin-27 displays interferon-γ-like functions in human hepatoma cells and hepatocytes

Herdis Bender, Monique Y. Wiesinger, Carolin Nordhoff, Caroline Schoenherr, Claude Haan, Stephan Ludwig, Ralf Weiskirchen, Nobuyuki Kato, Peter C. Heinrich, Serge Haan

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40 Citations (Scopus)

Abstract

Interleukin-27 (IL-27) is a cytokine belonging to the IL-6/IL-12 cytokine family. It is secreted by antigen-presenting cells, strongly acts on T cells, and also stimulates innate immune cells. In most studies, the effects of IL-27 on T cells were investigated; however, not much is known about possible effects of IL-27 on other cell types. IL-27 signals via the common IL-6 -type cytokine receptor chain gp130 and the IL-27 - specific chain WSX-1. Given the importance of gp130 in regulating liver responses such as the acute phase response or liver regeneration, we investigated whether IL-27 could also have a function in liver cells. We find that IL-27 stimulates hepatoma cells and hepatocytes by inducing a sustained signal transducer and activator of transcription (STAT)1 and STAT3 activation. Whereas the STAT3 mediated responses to IL-27 (γ-fibrinogen and hepcidin induction) are not detectable, we observe an interferon-gamma (IFN-γ) - like STAT1 response leading to the induction of interferon-regulated proteins such as STAT1, STAT2, interferon response factor (IRF)-1, IRF-9, myxovirus resistance A and guanylate binding protein 2. Conclusion: Our study provides evidence for a function of IL-27 in hepatoma cells and hepatocytes and shows that IL-27 responses are not restricted to the classical immune cells. Our results suggest that IL-27 exerts IFN-like functions in liver cells and that it can contribute to the antiviral response in these cells.

Original languageEnglish
Pages (from-to)585-591
Number of pages7
JournalHepatology
Volume50
Issue number2
DOIs
Publication statusPublished - Nov 26 2009

ASJC Scopus subject areas

  • Hepatology

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    Bender, H., Wiesinger, M. Y., Nordhoff, C., Schoenherr, C., Haan, C., Ludwig, S., Weiskirchen, R., Kato, N., Heinrich, P. C., & Haan, S. (2009). Interleukin-27 displays interferon-γ-like functions in human hepatoma cells and hepatocytes. Hepatology, 50(2), 585-591. https://doi.org/10.1002/hep.22988